This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Some studies have suggested that there are large gender differences in how women and men process and respond to emotional information. More recently there has been a great deal of research concerning the sexual dimorphism of an area of the brain called the amygdala. The amygdala is involved in the recall of emotional and arousing memory. These studies have concluded that emotional memory is processed in different hemispheres of the amygdala by men and women. In women amygdala activation occurs in the left hemisphere when encoding emotion memory and in the right hemisphere of the amygdala with in men. In addition, several studies have suggested that there may be a neurobiological underpinning to transgender identity that suggests that transgender individuals have biological organization more similar to their gender identity than to their biological sex. Prior research conducted on brain lateralization in transsexuals has reported that transsexuals have cerebral brain lateralization in congruence with their gender identity rather than biological sex. Understanding why there are gender differences in how the brain processes and remembers emotional information is important because there are a number of psychiatric disorders that have large gender differences and also involve the impaired processing of emotional information. Two examples of disorders that involve emotional dysregulation and affect one sex more than the other are depression and post traumatic stress disorder (PTSD). Depression occurs in 20 percent of women compared to 10 percent of men. The exact reason for this sex difference is unknown, however it is suggested that it is due to sex related differences in brain structures and functioning, as well as cognitive functions and styles. It has also been suggested that elevated physiological activity in the amygdala appears to be implicated in emotional behavior. Other research has found that depression is linked to enhanced activity of the left amygdala predominantly found in women. It has been reported that the trans community have higher than the average rates of depression and that their risk of suicide is also higher. This higher incidence of depression is largely influenced by societal norms and beliefs which are in part influenced by the notion that there is no biological cause underlying transgender identity. Therefore, the link between the amygdala processing of emotional information and gender is of utmost importance for the trans community due their higher than average risk of depression. It is important to further investigate the neurobiology of the amygdala and its relationship to depression, as well as understanding its functioning in everyone, including transgender individuals. Learning more about the neurobiology of gender differences in emotional memory and related brain activation will be important for the future development of treatments for these clinical disorders. This proposal will describe a study to examine emotional memory and related brain activation in transgender subjects both on and off hormones in order to learn more about the relationship between biological sex, hormones and the sexually dimorphic pattern of brain activation observed for remembering emotional information. This is a brain imaging study examining the patterns of brain activation during emotional memory tests in transgender individuals. Two groups of transgender individuals will be studied, 12 male to female transgender and 12 female to male transgender. Within each group 6 participants will be taking hormone treatment and 6 will not. Each participant will participate in one study day in which we will use fMRI to assess their amygdale activation during emotional memory encoding. The knowledge gained from this study will provide important information about the neurobiological underlying of gender differences in emotional memory, as well as in transgender individuals, while furthering knowledge about gender influenced psychiatric disorders.